Department Of Human Genetics And Molecular Medicine
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Item Genetic variants of metabolism and inflammatory pathways, and PCOS risk �Systematic review, meta-analysis, and in-silico analysis(Elsevier B.V., 2023-09-14T00:00:00) Sharma, Priya; Bhatia, Kabir; Singh Kapoor, Harmanpreet; Kaur, Balpreet; Khetarpal, PreetiImportance: Identification of genetic risk factors for PCOS susceptibility. Objective: To identify genetic risk variants of the genes involved in metabolic or inflammatory pathways. Data sources: Relevant literature was identified and extracted from PubMed, Central Cochrane Library, Google Scholar, and Science Direct by using a set of keywords related to pre-determined genes up to 06 May 2023. Study selection and synthesis: PRISMA guidelines were followed to design the protocol which is registered in PROSPERO (CRD42023422501). Pooled odds ratio (OR) and 95% confidence interval (95% CI) for different gene variants were calculated under different genetic models (dominant model, recessive model, additive model, and allele model) by using Review Manager software 4.2. Main outcomes: Metabolic genetic variants FTO rs9939609, IL-6 rs1800795 and CAPN10 rs3842570, rs2975760, and RAB5B rs705702 are associated with PCOS risk. Results: Forty-four relevant articles have been identified for genes involved in metabolic (n = 23) or inflammatory pathways (n = 21). There is a significant association (p < 0.05) of IL-6 rs1800795 and FTO rs9939609 with increased risk.CAPN10 rs2975760 Ins allele is suggested as a protective factor among only the non-Asian population. Also, a significant association of CAPN10 rs2975760 and RAB5B rs705702 with increased risk among the Asian population is suggested. However, no significant association could be found between CAPN10 rs3792267, rs5030952, and SUMO1P1 rs2272046, and the risk of PCOS in any of the subpopulations analysed. In silico analysis suggests the deleterious effect of IL-6 rs1800795. Conclusion: and relevance: The study suggests the role of various genetic variants for genetic predisposition to PCOS among different subpopulations. � 2023 Elsevier B.V.Item Differential molecular mechanistic behavior of HDACs in cancer progression(Springer, 2022-08-16T00:00:00) Singh, Tashvinder; Kaur, Prabhsimran; Singh, Paramdeep; Singh, Sandeep; Munshi, AnjanaGenetic aberration including mutation in oncogenes and tumor suppressor genes transforms normal cells into tumor cells. Epigenetic modifications work concertedly with genetic factors in controlling cancer development. Histone acetyltransferases (HATs), histone deacetylases (HDACs), DNA methyltransferases (DNMTs) and chromatin structure modifier are prospective epigenetic regulators. Specifically, HDACs are histone modifiers regulating the expression of genes implicated in cell survival, growth, apoptosis, and metabolism. The majority of HDACs are highly upregulated in cancer, whereas some have a varied function and expression in cancer progression. Distinct HDACs have a positive and negative role in controlling cancer progression. HDACs are also significantly involved in tumor cells acquiring metastatic and angiogenic potential in order to withstand the anti-tumor microenvironment. HDACs� role in modulating metabolic genes has also been associated with tumor development and survival. This review highlights and discusses the molecular mechanisms of HDACs by which they regulate cell survival, apoptosis, metastasis, invasion, stemness potential, angiogenesis, and epithelial to mesenchymal transitions (EMT) in tumor cells. HDACs are the potential target for anti-cancer drug development and various inhibitors have been developed and FDA approved for a variety of cancers. The primary HDAC inhibitors with proven anti-cancer efficacy have also been highlighted in this review. � 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Item Small regulatory molecules acting big in cancer: Potential role of mito-miRs in cancer(Bentham Science Publishers, 2019) Sharma P.; Bharat; Dogra N.; Singh S.MicroRNAs [miRNAs] are short, non-coding, single stranded RNA molecules regulating gene expression of their targets at the posttranscriptional level by either degrading mRNA or by inhibiting translation. Previously, miRNAs have been reported to be present inside the mitochondria and these miRNAs have been termed as mito-miRs. Origin of these mito-miRs may either be from mitochondrial genome or import from nucleus. The second class of mito-miRs makes it important to unravel the involvement of miRNAs in crosstalk between nucleus and mitochondria. Since miRNAs are involved in various physiological processes, their deregulation is often associated with disease progression, including cancer. The current review focuses on the involvement of miRNAs in different mitochondrial mediated processes. It also highlights the importance of exploring the interaction of miRNAs with mitochondrial genome, which may lead to the development of small regulatory RNA based therapeutic options.Item Assessment of soybean inhibitor as a biopesticide against melon fruit fly, Bactrocera cucurbitae (Coquillett)(Springer Berlin Heidelberg, 2017) Kaur, Harpreet; Kaur, Amandeep; Kaur, Amrit Pal; Rup, Pushpinder J.; Sohal, Satwinder K.In the current study, the soybean trypsin?chymotrypsin inhibitor (Bowman?Birk Inhibitor, SBBI) was tested against Bactrocera cucurbitae (Coquillett), a major pest of cucurbit crops. Bioassays conducted using different concentrations (12.5, 25, 50, 100 and 200?ppm) revealed a detrimental effect of the inhibitor on the growth and development of the second instar larvae of the melon fruit fly. SBBI prolonged the larval and total development period and reduced the percentage pupation and emergence. Enzymatic assays of proteases conducted at three time intervals using the LC40 (59?ppm) concentration of SBBI showed an inhibitory effect on trypsin activity, whereas an increase was observed in the activity of chymotrypsin, elastase and leucine aminopeptidase. Among the enzymes involved in detoxification, antioxidant and general metabolism, an increase was observed in the activity of catalases, and acid and alkaline phosphatases at most treatment intervals. The activity of esterases was induced only with prolonged treatment whereas that of glutathione S-transferases was suppressed in larvae treated with SBBI. The findings revealed the potential of SBBI to disrupt the growth of the melon fruit fly. ? 2017, Deutsche Phythomedizinische Gesellschaft.Item A low frequency variant within the GWAS locus of MTNR1B affects fasting glucose concentrations: Genetic risk is modulated by obesity(2012) Been, L.F.; Hatfield, J.L.; Shankar, A.; Aston, C.E.; Ralhan, S.; Wander, G.S.; Mehra, N.K.; Singh, J.R.; Mulvihill, J.J.; Sanghera, D.K.Two common variants (rs1387153, rs10830963) in MTNR1B have been reported to have independent effects on fasting blood glucose (FBG) levels with increased risk to type 2 diabetes (T2D) in recent genome-wide association studies (GWAS). In this investigation, we report the association of these two variants, and an additional variant (rs1374645) within the GWAS locus of MTNR1B with FBG, 2h glucose, insulin resistance (HOMA IR), ?-cell function (HOMA B), and T2D in our sample of Asian Sikhs from India. Our cohort comprised 2222 subjects [1201 T2D, 1021 controls]. None of these SNPs was associated with T2D in this cohort. Our data also could not confirm association of rs1387153 and rs10830963 with FBG phenotype. However, upon stratifying data according to body mass index (BMI) (low ? 25 kg/m2 and high > 25 kg/m2) in normoglycemic subjects (n = 1021), the rs1374645 revealed a strong association with low FBG levels in low BMI group (? = -0.073, p = 0.002, Bonferroni p = 0.01) compared to the high BMI group (? = 0.015, p = 0.50). We also detected a strong evidence of interaction between rs1374645 and BMI with respect to FBG levels (p = 0.002). Our data provide new information about the significant impact of another MTNR1B variant on FBG levels that appears to be modulated by BMI. Future confirmation on independent datasets and functional studies will be required to define the role of this variant in fasting glucose variation. ? 2011.